Mechanism of sulfotransferase pharmacogenetics in altered xenobiotic metabolism

Abstract

Introduction: Cytosolic sulfotransferases (SULTs), one of the vital enzymes of detoxication, catalyze the sulfation of native and exogenous hydrophobic molecules. Xenobiotic accumulation can induce a variety of diseases, including cancers. Sulfation facilitates the solubilization and removal of xenobiotics. However, sulfation may activate the pharmacological activities of xenobiotics.

Areas covered: The purpose of this review was to correlate the sequence, structure and function of SULTs. We focused on understanding the sulfation mechanisms of SULT through its sequence variation. We selectively reviewed SULT drug substrates, explained the enzyme-catalyzed sulfation reaction and its kinetic mechanisms, and the effect of amino acid sequence variation, such as single-nucleotide polymorphism, on the enzyme function.

Expert opinion: A wealth of information is available in the literature for understanding the detailed mechanisms underlying xenobiotic sulfation. We reviewed information regarding the sequence, structure and reaction mechanism of SULTs and explained how SULT activities altered. In addition to revealing the SULT kinetics, the mRNA expression of specific SULTs in tissues that revealed their distribution in tissues also affects overall SULT activities. Understanding of the structure–function relationship and the reaction mechanism of SULTs is valuable for understanding, preventing and treating diseases.

Keywords:

• single-nucleotide polymorphism
• substrate selectivity
• sulfotransferase
• xenobiotic metabolism

Acknowledgments

C-C Wang, Y-H Hou and Y-C Mao contributed equally to this work.

Declaration of interest

This work was supported by the Ministry of Science and Technology, Taiwan (103-2627-M-009-002 and 102-2311-B-009-004-MY3). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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